Others bind to prothrombin, factor Xa, and protein S promoting coagulation.19

In clinical care, the performance of the intrinsic system is measured by the partial thromboplastin time (PTT) and the performance of the extrinsic system by the prothrombin time (PT).3 Thrombin–antithrombin complex is an indirect indicator of a systemically activated coagulation system and can be clinically useful. Higher values indicate an increase in thrombin generation, a reflection of a procoagulant diathesis.20

A straightforward understanding of the clotting pathway does not translate directly into clinical insight. For example, intuition suggests that a deficiency of factor VII would predispose to a bleeding disorder, but paradoxically, a genetic deficiency of factor VII is thrombophilic.9 Some factors, such as factor XII, are involved in both the coagulation pathway and the fibrinolysis pathway. Nevertheless, a deficiency of factor XII overall is prothrombotic.21 When antiheparin antibodies develop after heparin therapy, the induced thrombocytopenia does not lead to increased bleeding as intuition would suggest, but rather to thrombosis, presumably because the antiheparin–platelet antibody also activates the clotting cascade.22 Finally, thrombosis is a critical part of the pathophysiology of RVO, but there are many cases of RVO developing in patients taking warfarin, aspirin, other platelet-aggregation inhibitors, and combinations of various anticoagulant drugs.

Beyond the acute stage of thrombosis, slower changes continue to occur. From 7 to 14 days after acute thrombosis, fibroblasts, endothelial cells, and inflammatory cells invade the clot. From 3 to 8 months recanalization of the clot occurs.10,26

2.1.2 Viscosity of Blood

Generally, viscosity is the resistance to flow of a fluid caused by friction between adjacent layers of the fluid. A precise definition is the ratio of the applied force (shear stress) to the differential

velocity of two layers of fluid (shear rate). For simple, or Newtonian, fluids such as water and plasma, the rate of flow under nonturbulent conditions is directly proportional to the applied force. Viscosity depends on temperature, increasing as the temperature decreases. Newtonian fluids are assigned a relative viscosity defined as their viscosity divided by the viscosity of water at the same temperature. Plasma at 37°C has a relative viscosity of 1.8.

For complicated, or non-Newtonian, fluids such as blood, the relationship of shear force to differential velocity of the fluid layers is dependent on the shear rate as a result of molecular interactions among the cellular components, electrolytes, and proteins. A lower shear rate increases viscosity. The main determinants of blood viscosity are hematocrit and plasma fibrinogen. The greater the number of red cells per unit volume, the larger the aggregates of red cells. Fibrinogen is the linking molecule in the red cell aggregates.27 Blood viscosity increases exponentially as the hematocrit increases (Fig. 2.3).29 Greater rigidity of erythrocytes, as in local acidosis or sickling, also increases viscosity.27 Other variables including age, time of day, and posture influence blood viscosity in less well-defined ways.30

Measured in viscometer

Hematocrit, %

Fig. 2.3 Graph of the dependence of relative viscosity of blood on hematocrit (Redrawn from Whittaker and Winton28)